Large Population Research Articles

Serum microRNA qPCR profiling and validation indicate upregulation of circulating miR-145-5p and miR-26a-5p in migraineurs

Abstract Background In recent years, miRNAs found in biological fluids have gained interest as biomarkers of numerous conditions, including migraine. This study aimed to identify differences in the levels of circulating miRNAs in the serum of migraineurs as compared to healthy controls, as well as between patients with different types of migraine and during the ictal and nonictal phases of the condition. Methods The screening phase of the study included serum from 13 migraine patients and 13 sex and age matched controls. A panel of 179 miRNAs was analysed using locked nucleic acid SYBR based qPCR. Based on statistical analysis (U Mann-Whitney test) and data from existing literature, nine miRNAs were selected for validation by TaqMan qPCR in an independent cohort of 26 migraineurs and eleven healthy controls. For comparison between the study and control group, U Mann-Whitney test was performed. The differences between patients with chronic and episodic migraine, migraine with and without aura and in ictal and nonictal phases were analysed with Kruskal-Wallis test. The results were corrected for multiple comparisons using Benjamini-Hochberg method. In all analysis p value ≤ 0,05 was considered as significant. Results Two miRNAs, miR-145-5p and miR-26a-5p were significantly upregulated in serum of migraineurs compared to healthy controls. MiRNA-19a-3p was downregulated in patients currently experiencing migraine headache compared to those in the interictal period. No differences were found between patients with different migraine types. Conclusion The results of our study add to the growing body of evidence for dysregulation of the circulating miRNA profile by migraine. They are further supported by previous reports on differential expression of miR-145-5p, miR-26a-5p and miR-19a-3p in migraineurs. However, more research on larger populations is needed to validate these findings, as well as elucidate the role of circulating miRNAs in the condition. Moreover, to wholly explore the biomarker potential of miRNAs, migraine patients should not only be compared to healthy controls but also to populations with different headache disorders. Graphical Abstract

Abstract A038: A targetable tumor-induced wound-healing response is essential for osteosarcoma lung metastasis

Abstract Lung metastasis is responsible for nearly all deaths in children and teenagers affected by osteosarcoma, the most common pediatric sarcoma. The mechanisms by which malignant bone cells manipulate the lung microenvironment to promote the colonization and growth of metastatic tumor cells remain unclear but represent a potential therapeutic opportunity for preventing and treating metastasis. In this study, we sought to understand how osteosarcoma cells educate the lung microenvironment during metastatic progression. To address this gap, we generated several time series datasets of niche-labeled, single-cell RNA-seq of developing metastatic lesions and then used these to characterize the changes occurring in tumor and tumor-associated stromal cells during colonization. After identifying candidate mechanisms, we tested several therapeutic interventions to evaluate their effects on metastasis development in vitro using a tumor-on-lung co-culture system and in vivo using our animal models. Osteosarcoma cells induced acute epithelial injury upon lung dissemination. Shortly after dissemination, a paracrine loop established between a hyper-secretory, hypo-proliferative subpopulation of tumor cells and alveolar epithelial cells triggers the adoption of a chronic, non-resolving wound phenotype within the surrounding tissues that culminates in extensive tissue fibrosis with persistent extracellular matrix deposition, especially fibronectin. Cellular changes observed during this process include the proliferation of type 2 alveolar epithelial cells, the accumulation of highly fibrogenic epithelial intermediates (analogous to those observed in pulmonary fibrosis), and the emergence of a large population of scar-promoting macrophages. The formation of this matrix seems essential for lesion formation—disruption of the matrix-tumor cell interaction eliminated pseudonodules in vivo. Inhibition of pro-fibrotic pathways using nintedanib, an FDA- approved drug used to treat pulmonary fibrosis, or of tumor-epithelial paracrine signals with anakinra, an antagonist of IL1 signaling, effectively blocked metastatic lesion growth in both murine and human xenograft models, showing evidence of microenvironment reprogramming in the single cell data. Combining these therapies, which target primarily the hyper-secretory, hypo-proliferative “anchor” cells, with conventional therapies, which target proliferating tumor cells, proved highly effective in eliminating established metastatic lesions. Our work demonstrates that disseminated osteosarcoma cells trigger an aberrant, non-resolving wound-healing response in tumor-associated lung tissues, similar to that observed in non-malignant pulmonary fibrosis, and that this pathologic wound-healing response promotes metastatic growth. Therapeutic disruption of fibrosis-associated signaling prevents metastasis and treats established metastatic disease in multiple osteosarcoma models. Citation Format: James B. Reinecke, Leyre Jimenez Garcia, Amy C. Gross, Matthew V. Cannon, Yogesh Budhathoki, Ryan D. Roberts. A targetable tumor-induced wound-healing response is essential for osteosarcoma lung metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A038.

Initiating continuous glucose monitoring is associated with improvements in glycemic control and reduced health care resource utilization for people with diabetes in a large US-insured population: A real-world evidence study.

To examine the real-world impact of continuous glucose monitoring (CGM) use on glycemic management and health care resource utilization (HCRU) in people with diabetes in a large US-insured population. This retrospective observational study used Aetna administrative claims data from a cohort of fully insured commercial and Medicare Advantage beneficiaries with diabetes and with coverage for medical and pharmacy benefits. The index date was the first CGM pharmacy or medical claim observed between January 1, 2019, and December 31, 2021. Change in hemoglobin A1c was calculated using values from 3 months before and the latest values 10-12 months after the index date. HCRU was measured 12 months before and after the index date. Data were analyzed by the following patient groups: type 1 diabetes, type 2 diabetes (T2D) on intensive insulin therapy, T2D on basal-only insulin therapy, and T2D not on insulin therapy. Data from 7,336 patients (74% T2D, mean age 57 years, 42% Medicare-insured, 54% male, 56% White) were analyzed. Beneficiaries with available A1c data (n = 1,063) showed a significant improvement in A1c after CGM initiation (-0.7%, P < 0.0001), including -0.9% change in the T2D not on insulin group (n = 264). For the overall cohort, the number of patients with diabetes-related hospitalizations and emergency department visits decreased significantly by 67% and 40%, respectively (P < 0.0001 for both). This study showed that CGM use was associated with clinically meaningful improvements in A1c and reduced HCRU, suggesting potential for population-level clinical benefits, especially for patients not using insulin.

Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case-control study within the E3N-Generations cohort.

Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk. We used data from a nested case-control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects). The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00-5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13-4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93-4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05-1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75-1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol. Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.

A Single-Cell Interrogation System from Scratch: Microfluidics and Deep Learning.

Live-cell imaging using fluorescence microscopy enables researchers to study cellular processes in unprecedented detail. These techniques are becoming increasingly popular among microbiologists. The emergence of microfluidics and deep learning has significantly increased the amount of quantitative data that can be extracted from such experiments. However, these techniques require highly specialized expertise and equipment, making them inaccessible to many biologists. Here we present a guide for microbiologists, with a basic understanding of microfluidics, to construct a custom-made live-cell interrogation system that is capable of recording and analyzing thousands of bacterial cell-cycles per experiment. The requirements for different microbiological applications are varied, and experiments often demand a high level of versatility and custom-designed capabilities. This work is intended as a guide for the design and engineering of microfluidic master molds and how to build polydimethylsiloxane chips. Furthermore, we show how state-of-the-art deep-learning techniques can be used to design image processing algorithms that allow for the rapid extraction of highly quantitative information from large populations of individual bacterial cells.

Prognostic Factors in Patients Undergoing Physiotherapy for Chronic Low Back Pain: A Level I Systematic Review

Background: Low back pain is common. For patients with mechanic or non-specific chronic LBP (cLBP), the current guidelines suggest conservative, nonpharmacologic treatment as a first-line treatment. Among the available strategies, physiotherapy represents a common option offered to patients presenting with cLBP. The present systematic review investigates the prognostic factors of patients with mechanic or non-specific cLBP undergoing physiotherapy. Methods: In September 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the randomised controlled trials (RCTs) which evaluated the efficacy of a physiotherapy programme in patients with LBP were accessed. All studies evaluating non-specific or mechanical LBP were included. Data concerning the following PROMs were collected: the pain scale, Roland Morris Disability Questionnaire (RMQ), and Oswestry Disability Index (ODI). A multiple linear model regression analysis was conducted using the Pearson Product–Moment Correlation Coefficient. Results: Data from 2773 patients were retrieved. The mean length of symptoms before the treatment was 61.2 months. Conclusions: Age and BMI might exert a limited influence on the outcomes of the physiotherapeutic management of cLBP. Pain and disability at baseline might represent important predictors of health-related quality of life at the six-month follow-up. Further studies on a larger population with a longer follow-up are required to validate these results.

Multimodal Biometric Authentication System for Military Weapon Access: Face and ECG Authentication

Unimodal or Single factor biometric systems refer to biometric systems that employ only one form of biometric data to authenticate an individual’s identity. These kinds of biometrics are susceptible to higher error rates and security vulnerabilities because it relays on a single trait for authentication. To overcome this, multimodal biometrics method is proposed. Multi-modal biometric system can authenticate more than once and some advantages include; highaccuracy, low error rate, and large population coverage. These biometrics systems increase integrity and privacy since it will contain several biometric features of every customer. So, here designed a multimodal biometrics project utilizing deep learning to enhance authentication security by combining face and Electrocardiogram(ECG) signals. VGG-16 model, a deep learning architecture used to capture complex patterns in accurate individual identification with both ECG and Facial data. The high-resolution convolutional filters capture the intricate details of the face and ECG waveform, ensuring high accuracy in distinguishing different individuals.

Abstract PR009: Application of Liquid Biopsy-RECIST (LB-RECIST) criteria to track metastatic colorectal cancer (mCRC) molecular response in first-line (1L) setting: Findings from the PLATFORM-B study

Abstract Introduction: Circulating tumor DNA (ctDNA) analysis is a minimally invasive and reproducible method to explore tumor molecular biology. Recently, Gouda et al. proposed the LB-RECIST criteria to monitor molecular response, validating them on a heterogeneous metastatic population. However, data on mCRC are lacking. Here, we report the first attempt to apply LB-RECIST in the multicenter prospective PLATFORM-B study, which enrolled 130 mCRC patients (pts) receiving 1L standard therapy, with ctDNA analysis performed at different time points. Materials and Methods: Baseline (BL) and week 8 (W8) plasma samples were analyzed using a targeted NGS-based approach (Ion S5 system). Changes in ctDNA detectability were assessed to determine molecular response as per qualitative LB-RECIST criteria: Group1 (G1, detectable ctDNA at BL and W8); Group2 (G2, detectable BL and undetectable W8); Group3 (G3, undetectable BL and detectable W8); Group4 (G4, undetectable at BL and W8). Changes in aggregate variant allele frequency (VAF) - the sum of all VAFs of the studied genes in a sample - were used to assess quantitative LB-RECIST responses: ctDNA Complete Response (CCR, clearance after initial detectability), Partial Response (CPR, decrease &amp;gt;10%), Stable Disease (CSD, no change or decrease &amp;lt;10%), Progressive Disease (CPD, increase &amp;gt;10% or new mutations), and Non-measurable Disease (CND, undetectable at BL and W8). Molecular results were correlated with clinical outcomes. Statistically significant differences were assessed across different groups using 2-sided P values with an α ≤ .05 level of significance. Results: Overall, 79 pts had paired BL and W8 samples. Quantitative LB-RECIST identified 32 CCR, 18 CND, 20 CPR, 8 CPD, and 1 CSD cases. Qualitative LB-RECIST found 22 G1, 32 G2, 7 G3, and 18 G4 cases. Radiological RECIST identified 6 CR, 47 PR, 21 SD, and 5 PD. CCR showed the highest survival rates: with a median follow-up of 25 months (mo) (range: 1–49), median progression-free survival (mPFS) was not reached (NR) and median overall survival (mOS) was 41.8 mo. The CND group had similar rates (mPFS NR; mOS 41.1 mo). CPR and CPD had the poorest outcomes: for CPR, mPFS was 12.7 and mOS 16.4 mo; for CPD, mPFS and mOS were 11.9 and 25.5 mo, respectively. In the G1, G2, G3, and G4 groups, mPFS was 11.9, NR, 14.2, and NR, respectively, while mOS was 16.4, 41.8, 33.4, and 41.1 mo. Kaplan-Meier analysis of the quantitative groups showed statistically significant differences (P &amp;lt; .0001) for both PFS and OS curves. The same level of significance was found in the qualitative groups. Conclusion: LB- RECIST can be a rapid and reproducible method to assess molecular response in mCRC. However, concerns remain. The CND group (23% of cases) showed survival rates similar to the CCR group, as observed also between G4 and G2. These data suggest that absence of ctDNA at W8 is the best surrogate for OS. Moreover, CPD had higher OS rates than CPR, but similar PFS. Further investigations in larger populations are needed to refine these criteria and improve molecular response stratification Citation Format: Valentino Martelli, Joana Vidal, Maria Concepción Fernández-Rodríguez, Pilar García-Alfonso, David Páez, Joan Gibert, Jennifer Linares, Annarita Sibilio, Vicente Alonso, Maria Teresa Cano, Cristina Santos, Gema Duran, Elena Élez, José Luis Manzano, Rocio Garcia-Carbonero, Reyes Ferreiro, Ferran Losa, Estela Pineda, Javier Sastre, Auxiliadora Gomez-España, Rodrigo Toledo, Fernando Rivera, Beatriz Bellosillo, Josep Tabernero, Ramon Ramon Salazar, Enrique Aranda, Clara Montagut. Application of Liquid Biopsy-RECIST (LB-RECIST) criteria to track metastatic colorectal cancer (mCRC) molecular response in first-line (1L) setting: Findings from the PLATFORM-B study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR009.

Cultivating partnerships to incorporate health promotion modules into primary school curricula: a case study in France

School-based health promotion (HP) emerged from the settings-based approach. Children from disadvantaged neighborhoods benefit from HP in their school. Teachers deliver HP modules but need additional resources. This case study aimed to form a transdisciplinary partnership in a socially disadvantaged area to co-develop and embed HP modules into existing curricula. A 3-stage framework was used in this study. Stage 1 cultivated partnerships, reviewed evidence and existing data. Stage 2 generated ideas and co-developed HP modules. Stage 3 trialed the modules within primary school classrooms. Stage 1 resulted in a partnership between city authorities, a primary school and a comprehensive cancer center all located in the same community in France. The reviewed data and evidence provided 18 examples of school-based HP programs and showed that the school is in a highly disadvantaged neighborhood with a large immigrant population. Stage 2 developed 3 HP modules: “Taste and Science Week,” “Nutrition Weeks,” and “Breakfast Week,” each embedded as add-ins into existing math and science lessons and workshops. Finally, stage 3 trialed the modules in 10 first to fifth grade classrooms impacting 214 total students. Transdisciplinary partnerships help co-create and support evidence-driven HP programs. This collaborative approach enabled primary school teachers to effectively embed the HP modules into pre-existing math and science curricula. Families and volunteers are an integral part of successful HP programs however, limited participation was a challenge. Further research is needed to evaluate indicators such as student academic success and health behavior change.

Adoption of Paramparagat Krishi Vikas Yojana by Farmers in Bikaner District of Rajasthan, India

India's diverse heritage and rich culture are well-known throughout the world. When time passed and the population suddenly increased, farmers were obliged to utilise various agro-chemicals to feed the large population, even though they had previously grown a variety of crops without the use of these pesticides. In Bikaner district of Rajasthan state, coarse cereals are mostly grown without using any chemicals because Bikaner is a water scarce area and prone to crop failure hence farmer generally does not spend so much money on chemicals like fertilizers, insecticide-pesticides, herbicides etc. Looking to the virginity of land, the Rajasthan government has launched the Paramparagat Krishi Vikas Yojana (PKVY) in this district. As a result, the greatest numbers of clusters under PKVY were developed during 2015-18. Thus, the study was carried out in the purposely chosen Bikaner District of Rajasthan state in order to gauge the respondents' level of adoption of PKVY. There are eight tehsils in the Bikaner district; three tehsils, Nokha, Sridungarhgarh, and Bikaner, were specifically chosen for the current study due to the maximum number of clusters formed under PKVY. A total of 180 respondents, out of which 90 beneficiary who were registered in PKVY selected by using proportionate random sampling method and to constitute the other half of sample size same number of farmers i.e. 90 were also selected randomly from the same villages who have not registered in PKVY and they were called as non-beneficiary respondents included in the current investigation. The results of the study concluded that majority of the respondents had medium level of extent of adoption of PKVY in the study area. They had highest extent of adoption on the aspect of “nutrient management” and least extent of adoption of “technical knowledge”. There was significant association found between education, mass media exposure, information seeking behaviour, information sharing behaviour and knowledge of respondents about PKVY.

Evaluating the efficacy of a mindfulness mobile app for stress reduction in nurses

Objective: All Nurses experience work stress that can take their focus away from patient care. Healthcare organizations strive to identify successful, cost-effective stress reduction programs. Mindfulness Based Stress Reduction (MBSR) training is a validated approach to stress reduction, usually in a class format. However, financial and time constraints make it inaccessible to most practicing nurses. Alternatively, mobile mindfulness apps offer an approach to mindfulness that can reach large populations, are available 24/7, anonymous, and cost effective.Methods: This prospective, study evaluated the efficacy of a mindfulness mobile app for stress reduction in nurses utilizing Whil, a Mobile App that offers mindfulness training specifically geared towards health professionals. Eight hundred and fifty-two nurses were recruited from twelve sites (71 per site) within a large Health Care System in the Northeast United States.Results: Two scales were used to test results. Nurses Stress Scale (NSS) results indicated that nurses experienced a reduction in stress level with use and time spent in the app. Nurses in the 31-40 age range and nurses on 12-hour shifts experienced greater stress levels.Conclusions: Significant differences were seen in the Subscales Conflict with Physicians, Conflict with other Nurses, and Lack of Support. There was no change in the Mindfulness Attention Awareness Scale (MAAS) over time. Spearman’s correlation showed a significant and negative correlation between NSS and MAAS scores. The Whil Mobile App is effective for stress reduction in practicing nurses on all shifts and is cost effective.

Colour vision deficiency is associated with increased prevalence of amblyopia, strabismus and ametropia: a large population study

AimsTo examine the association between colour vision deficiency (CVD) and other ophthalmic disorders including amblyopia, strabismus and ametropia in a large population study.MethodsThe retrospective, cross-sectional study included 916 388 Israeli...

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p&lt;0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Abstract 4136755: Associations of Pulmonary Hypertension and Lung Cancer: A Prospective Cohort Study of Half a Million UK Biobank Participants

Background: Pulmonary hypertension (PH) and lung cancer (LC) are both significant public health issues with substantial morbidity and mortality. Recent studies suggest potential associations between pulmonary vascular diseases and LC due to shared risk factors and pathophysiological mechanisms, yet comprehensive research in large populations is scarce. Methods: This prospective cohort study utilized data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until November 30, 2023, for England and Scotland, and May 31, 2022, for Wales. We included 6,425 participants with LC, identified using linked cancer registry data, and followed them for the incidence of PH over a period of 10 years. We adjusted for potential confounders including age, ethnics, sex, smoking status, BMI, and histologic subtypes of LC. Statistical analyses were performed using Time-dependent Cox proportional hazards models to estimate the associations between PH and LC. Results: Of 502,173 participants in this prospective cohort, 6,425 were diagnosed with LC, while 494,451 did not receive the LC diagnosis. The prevalence of PH in the LC cohort and the no-LC cohort were 0.64% (1,494 of 3,142 women [47.55%]) and 2.40% (59 of 154 women [38.31%]), respectively, with significant difference between the two groups (p&lt;0.001). In the LC cohort, the mortality rates of patients without PH and with PH were 69.18% and 77.92% (p=0.020). Among the patients diagnosed with LC and PH, 33.12% were diagnosed with LC after PH (PH-LC), while 66.88% were diagnosed with LC before PH (LC-PH). And the mortality rates of the PH-LC group and the LC-PH group were 78.43% and 77.67%, respectively, with no significant difference between the two groups (p=0.915). Time-dependent Cox regression analysis showed that PH shows an increasing trend in risk (5th year HR: 3.22, 95% CI: 2.09-4.99, p-value &lt; 0.001), highlighting its significant impact on LC long-term prognosis. Conclusion: To conclude, the presence of PH significantly increased the risk of mortality in participants with LC, especially for the long-term LC survivors. And certain percentage of patients were diagnosed with LC before PH, but they had no significant difference between the patients with LC after PH.

Analisis Sentimen Masyarakat terhadap Pelayanan e-KTP dengan Metode Support Vector Machine

The rapid development of information and communication technology allows society to access various information needed in daily life. The Law of the Republic of Indonesia Number 23 of 2006 concerning population administration serves as an important element in population management. Population documents are issued by official institutions and have legal legitimacy as valid evidence. The method used in this research regarding public sentiment towards e-ID card services is the survey method, which aims to collect data from a large population using a smaller sample. The steps or processes in this research using the SVM method consist of case folding, cleaning, tokenizing, normalization, stopword removal, and stemming. Based on the classification of 150 test data using SVM, the number of positive sentiments recorded is 110 opinions, while negative sentiments recorded are 40 opinions.

Abstract 4137782: Fibrinogen-to-Albumin Ratio Does Not Correlate with Comprehensively Assessed Coronary Artery Disease Severity or High-Risk Plaque Features on Coronary Computed Tomographic Angiography

Background: Fibrinogen-to-albumin ratio (FAR) has been proposed as a readily available inflammatory biomarker associated with coronary artery disease (CAD). However, its association with CAD severity and prognosis has predominantly been assessed in patients with acute coronary syndromes (ACS). The Leiden score is a validated comprehensive measure of CAD incorporating stenosis proximity, severity, and plaque type that independently predicts cardiovascular events. Whether FAR is associated with Leiden score or high-risk plaque features on coronary computed tomographic angiography (CCTA) in stable outpatients is unknown. Methods: Adult outpatients undergoing clinically indicated CCTA were enrolled (5/2021-9/2023) in a prospective study assessing the relationship of plaque to immune markers and provided same-day pre-scan peripheral venous blood samples. CCTAs were post-processed and analyzed by the consensus of two expert readers blinded to clinical data using a 17-segment model to determine coronary artery calcium (CAC), Leiden score, and high-risk plaque features. Patients were grouped by FAR (quartiles), Leiden score (&lt;5, 5-20, &gt;20), and CAC score (0, &gt;0-100, &gt;100-300, &gt;300-1000, &gt;1000). Numerical variables were compared via Wilcoxon and Kruskal-Willis tests. Spearman correlation was calculated between FAR and Leiden score. Results: Of 284 patients, 53.8% were male, 86.7% were white, and 58.8% were on a statin (Table 1). Median FAR was 70.3 mg/g, 64.0% had a non-zero CAC score, and 25.0% had at least one segment with one high-risk plaque feature. Across quartiles of FAR, there was no difference in Leiden score (5.8 (IQR: 0.0-18.5), 12.4 (3.1-20.7), 8.0 (0.0-19.9), 6.8 (0.0-21.1), p=0.50) or probability of having at least one segment with at least one (29.6%, 23.9%, 23.9%, 22.5%, p=0.69) or two (18.3%, 14.1%, 12.7%, 15.5%, p=0.66) high-risk plaque features. There was no correlation between FAR and Leiden score (R=0.03, p=0.66). There was no difference in FAR when stratified by Leiden score (Table 1, p=0.53), CAC score (Table 2, p=0.50), or number of segments with at least one high-risk plaque feature (Table 3, p=0.18). Conclusion: In a prospective cohort of adult outpatients across a wide spectrum of CAD burden with high rates of baseline statin use, FAR was not associated with CAD or presence of high-risk plaque features on CCTA. Further evaluation of its role as an inflammatory biomarker in larger populations, particularly patients without ACS, is required.

Abstract 4136916: Indobufen: A Viable Alternative to Aspirin for Antiplatelet Therapy in patients with Aspirin Intolerance

Introduction: Antiplatelet therapy with aspirin has been recommended for patients with stroke and myocardial infarction (MI). Clinicians face challenges when they come across aspirin hypersensitivity in their clinical practice. Therefore, potential alternative drugs can help avoid the omission of anti-thrombotic therapy. Indobufen is a cyclooxygenase-1 inhibitor studied as an alternative to aspirin. Hypothesis: Compared to aspirin, indobufen will be equally effective in preventing cardiovascular events in patients needing antiplatelet therapy but will cause fewer bleeding complications. Methods: We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing antiplatelet therapy with indobufen vs. aspirin. The efficacy outcomes of interest were composite vascular events, MI, and ischemic stroke. The safety outcomes of interest were major bleeding and any bleeding. Heterogeneity was assessed using I 2 statistics. Analysis followed the PRISMA guideline and was registered in the PROSPERO database (CRD42024540911). Results: The systematic review identified 4 studies, including 11,495 patients (indobufen n=5,728, 49.83%), with two studies in patients post-MI and two post-stroke patients. Composite vascular events at 90 days (RR 1.03; 95%CI 0.58-1.86; p=0.911; I 2 =46%) and 1 year (RR 1.10; 95%CI 0.96-1.27; p=0.184; I 2 =0%) did not show any difference between the groups. MI (RR 0.67; 95%CI 0.36-1.23; p=0.197; I 2 =0%) and ischemic stroke (RR 1.17; 95%CI 0.99-1.38; p=0.064; I 2 =0%) at 1 year did not show any significant difference between the groups. Major (RR 0.68; 95%CI 0.36-1.27; p=0.225; I 2 =74%) and any bleeding (RR 0.62; 95%CI 0.36-1.06; p=0.079; I 2 =91%) at 1 year were also comparable between the groups. Conclusion: Antiplatelet therapy with indobufen was comparable with aspirin in efficacy and safety. Indobufen can be considered an alternative to aspirin in patients with intolerance or hypersensitivity. However, more trials with a larger population are needed to confirm the clinical applicability.

Abstract 4113573: Long Noncoding RNAs to Predict COVID-19 Neuro-Cardio-Vascular Outcomes

Introduction/Background: Cardiovascular and neurological diseases develop in a significant proportion of COVID-19 patients. Minimally invasive tools to predict outcome after SARS-CoV-2 infection would enable personalized healthcare, potentially easing the disease burden. We showed that blood levels of the long noncoding RNA lymphoid enhancer-binding factor-1 antisense 1 (LEF1-AS1) predict COVID-19 in-hospital mortality. Hypothesis: LEF1-AS1 is associated with long-term clinical outcomes of COVID-19. Aim: Test the capacity of LEF1-AS1 to predict neuro-cardio-vascular outcomes post-SARS-CoV-2 infection. Methods/Approach: We enrolled 104 primo-infected COVID-19 patients aged 18+ recruited from April to December 2020 in the PrediCOVID national cohort for which 12-month follow-up data were available (Ethics Committee approvals 202003/07 and 202310/02-SU-202003/07). Whole blood samples were collected at baseline and expression levels of LEF1-AS1 were assessed by quantitative PCR. Results/Data: Of the 104 patients, 35 had at least one neurological symptom and one cardiovascular symptom at month 12. Levels of LEF1-AS1 at baseline were lower (p=0.019) in patients who developed neurological and cardiovascular symptoms as compared to patients who did not. Lower LEF1-AS1 was associated with symptoms development with an odds ratio of 0.48 (95% CI 0.28-0.83) from logistic regression model adjusted for age, sex, comorbidities and disease severity at baseline. Addition of LEF1-AS1 to a clinical model including age, sex, comorbidities and baseline severity yielded an incremental predictive value as attested by an increased AUC from 0.79 to 0.83 (likelihood ratio test p=0.005), a net reclassification index of 0.54 (p=0.007) and an integrated discrimination improvement of 0.08 (p=0.009). Conclusion: Blood levels of LEF1-AS1 predict 12-month neurological and cardiovascular outcomes of COVID-19 patients. This needs to be validated in larger populations.

Abstract 4137527: Evaluation of 10-Year Atherosclerotic Cardiovascular Risk Prediction Performance using the PREVENT versus Pooled Cohort Equations in a US Integrated Healthcare System

Background: The American Heart Association published the new PREVENT equations for estimating atherosclerotic cardiovascular disease (ASCVD) risk. Question: Do the PREVENT equations improve risk prediction for 10-year ASCVD compared with the pooled cohort equations (PCEs) in a large diverse population? Aim: To assess ASCVD risk prediction performance of the two PREVENT equations [PREVENT Base, PREVENT Base plus optional predictors including urine albumin-to-creatinine ratio, glycated hemoglobin, and social deprivation index (PREVENT Full)] compared with the PCEs. Methods: We included adults aged 40-75 years without a history of ASCVD or diabetes from Kaiser Permanente Southern California in 2009 and followed them through 2019. Outcome was incident ASCVD defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke. We compared model discrimination (Harrell’s C), mean calibration (estimated as the ratio of predicted to observed event rates), and calibration curve among the overall population and stratified by sex and race/ethnicity. Results: Of the 559,111 adults (mean age 54, 11% Black, 32% Hispanic), 10,695 developed an ASCVD event during a median follow-up of 10 years. Harrell’s C among the overall population was 0.741 (95% CI 0.736-0.745) for PREVENT Base, 0.743 (0.738-0.748) for PREVENT Full, and 0.741 (0.736-0.746) for the PCEs ( Table ). Compared with the PCEs, both PREVENT equations improved Harrell’s C in men but not in women, and in Black adults but not in other racial/ethnic groups. Both PREVENT equations were well-calibrated (mean calibration ranged 0.83-1.37; calibration slope ranged 0.71-1.28), while the PCEs overestimated 10-year ASCVD risk (mean calibration ranged 1.80-2.20; calibration slope ranged 0.34-0.45) ( Table &amp; Figure ). Conclusion: Compared with the PCEs, both PREVENT Base and Full equations improved calibration in predicting 10-year ASCVD risk, with minimal improvement in discrimination in men and Black adults only.

Clinical Evidence Regarding Spermidine–Hyaluronate Gel as a Novel Therapeutic Strategy in Vestibulodynia Management

Background: Vestibulodynia (VBD) represents a summation and overlapping of trigger factors (infections, hormonal disturbances, allergies, genetic aspects, psychological vulnerability, and others) with broad individual variability. As there are no standard treatment options for VBD, the disease is still in need of appropriate therapeutic tools. Objectives: A prospective observational trial was performed to confirm the efficacy of a topical gel containing a spermidine–hyaluronate complex (UBIGEL donna™) as either a stand-alone or companion treatment through a multicenter study on a large sample population. Methods: For women with VBD (n = 154), the treatment consisted of approximately two months (4 + 4 weeks) of applications according to the posology of UBIGEL. Evaluation of symptoms was performed on relevant clinical endpoints: dyspareunia and vulvovaginal pain/burning by a visual scale (VAS); vestibular trophism by a vestibular trophic health (VeTH) score; vulvoscopy through a cotton swab test; and the level of hypertonic pelvic floor by a physical graded assessment of levator ani hypertonus. Results: A total of 154 patients treated with UBIGEL donna™ showed significant improvements across all five evaluated parameters, including pain, dyspareunia, swab test results, muscle hypertonicity, and vestibular trophism. Pain and dyspareunia scores decreased by 46.5% and 33.5%, respectively, while significant improvements were also observed in the other parameters (p &lt; 0.0001). These improvements were consistent across various stratifications, including age and disease duration. Conclusions: The findings of the present study suggest that UBIGEL donna™ is effective in alleviating pain and dyspareunia, as well as reducing vestibular hypersensitivity in women with VBD. Although UBIGEL donna™ alone cannot serve as a comprehensive substitute for all recommended therapies, we suggest that multimodal therapy strategies may be crucial for attaining substantial improvement in any aspect of the condition.